1. Field of the Invention
This invention relates to a method and device for the controlled administration of drug to a patient. More particularly, this invention relates to a drug dispensing device which bioerodes in the biological environment of such patient. In preferred embodiments, the invention relates to a bioerodible device for the controlled and continuous administration of drug to a mammalian patient, especially to the eye of such patient, over a prolonged period of time. In another aspect the invention relates to a method for preparing these devices.
2. Description of the Prior Art
Many and varied compositions, products, appliances, depositors, applicators, dispensers and injectors are well known in the art in which the timing or spacing of administration or absorption of drug is regulated by the structure or physical arrangement of elements so that a single administration provides a gradual but sustained feeding of the drug to a patient by slow or differential release. The advantages of such devices are that they enable the physician to more carefully regulate the level of drug administration to the patient. A further advantage of sustained release devices is the fact that the number of times that the drug need be administered is reduced.
Where oral administration is desired, one means for obtaining the above objective is to employ capsules or tablets which release the drug at a uniform rate during the capsule's passage through the gastrointestinal tract. In the past this object has been achieved by admixing one or more inert ingredients with the drug in such a manner that these inactive materials interfere with the disintegration of the tablet or the dissolution of the drug. An obvious form of such a tablet is one wherein tablets can be composed of several alternate layers of medicament and inert material. In this manner, as each alternate protective layer disintegrates the patient receives a further dose of medicament. However, tablets of this type suffer from the disadvantage of not providing a uniform and constant drug release. Furthermore, such tablets are difficult to prepare with precision so that in many instances the desired dosage level cannot be assured. Moreover, it has not been possible to provide for prolonged release of a drug by these tablets because of their rapid rate of degradation or dissolution. Still further, degradable carriers of this type have not generally found wide acceptance because of the undesirable side effects which they often produce, for example, foreign body reaction and scar formation.
Recognizing these disadvantages, more recently there have been developed certain synthetic polymeric carriers, most notably the polysiloxane rubbers, which are designed to deliver a drug to the patient without concomitant degradation of the delivery device. Instead, the polymeric drug delivery systems are based upon the phenomenon of diffusion in which drug migrates through a polymer wall at a relatively low rate. In such a system, the drug is disposed throughout the polymeric carrier manufactured from the polymeric material.
In this regard, a significant advance has recently been made in the field of ophthalmic drug delivery systems. Thus, U.S. Pat. No. 3,416,530, granted Dec. 17. 1968 to Ness, entitled "Eyeball Medication Dispensing Tablet", and U.S. Pat. No. 3,618,604 issued Nov. 9, 1971 to Ness, entitled "Ocular Insert", disclose a drug dispensing ocular insert which releases controlled amounts of drug to the eye. These devices have the added advantage of permitting slow release of drug over prolonged periods of time. Such ocular inserts are fabricated of materials that are biologically inert, non-allergenic, and non-bioerodible in tear liquid. To initiate the therapeutic program, the ocular insert is placed in the upper or lower sac of the eye bounded by the surfaces of the sclera of the eyeball and conjunctiva of the lid. Since the material from which the ocular insert is formed is not erodible by tear liquid, it retains its integrity during the course of therapy, acting as a reservoir to continuously release drug to the eye and surrounding tissues at a controlled rate. A single such ocular insert can provide the complete ophthalmic dosage regimen for a particular time period, on the order of 24 hours or longer. More frequent repeated applications which are necessary with liquids, ointments, or water soluble lamellae are avoided. On termination of the therapeutic program the ocular insert is removed from the eye.
While the drug dispensing ocular inserts described above, which deliver precise amounts of drug to the eye continuously and in a controlled manner over a prolonged period of time, have proved to be markedly superior to the prior art ointments and liquids, there remain, however, improvements to be made. The ocular insert remains intact during the course of therapy and on termination of the therapy program must be removed, which may present difficulty and discomfort to some patients. In rare instances, the removal is made more difficult by unwanted migration of the insert to the upper fornix. Further, in ophthalmic practice physician-patient contact is often not of a sufficient degree to insure that instructions from the doctor are accurately carried out by the patient. Thus, when a non-erodible ocular insert is used, there is no certainty that the insert will be removed by the patient at the completion of treatment. This is particularly true with elderly patients who often forget or are simply unable to remove the device due to failing memory or eyesight.
Disadvantages of the same nature exist with drug delivery devices which are non-bioerodible employed in areas of the anatomy other than the eye in that at some point in time the device must be surgically or otherwise removed from the body of the patient.